Fundamentals of Medicinal Chemistry

A.2 Bacteria

Bacteria are microscopic plants varying in size from about 0.1 to 20. They are

usually unicellular and have a variety of shapes ranging from spheres to rods.

Most bacteria have a well defined cell wall that covers the outer surface of the

plasma membrane (see Appendix 3) of the cell. This is a rigid structure, consist-

ing of a complex polypeptide–polysaccharide (peptidoglycan, Figures A2.2 and

A2.3) matrix. It maintains the shape and integrity of the bacteria by preventing

either the swelling and bursting (lysis) or the shrinking of the bacteria when the

osmotic pressure of the surrounding medium changes. The bacterial cell wall is

continually being broken down by enzymes in the surrounding medium and so it

is continuously being rebuilt. This rebuilding process offers a potential target for

drugs since inhibition of the reconstruction processes could destroy the integrity

of the bacterial cell, resulting in its death.

Bacteria are commonly classified as being either Gram-positive or Gram-

negative depending on their response to the Gram stain test. The cell walls of

Gram-positive bacteria are about 25 nm thick and consist of up to 20 layers of

the peptidoglycan (Figure A2.1(a) ). In contrast, the cell walls of Gram-negative

bacteria are only 2–3 nm thick and consist of an outer lipid bilayer attached

through hydrophobic proteins and amide links to the peptidoglycan (Figure

A2.1(b)). This lipid–peptidoglycan structure is separated from the plasma mem-

brane by an aqueous compartment known as theperiplasmic space. This space

Peptidoglycan (cell wall)

Periplasmic space

Outer membrane,

consisting of

proteins,

lipopolysaccharides

and phospholipids.

Peptidoglycan (cell wall)

Cytoplasm

Plasma membrane

(a) Gram-positive bacteria (b) Gram-negative bacteria

Figure A2.1 Schematic cross-sections of the cell envelopes of (a) Gram-positive and (b) Gram-

negative bacteria

240 APPENDIX 2 BACTERIA